title: Inorganic mercury interacts with thiols at the nucleotide and cationic binding sites of the ouabain-sensitive cerebral electrogenic sodium pump.
abstract: The molecular events leading to neuronal dysfunction often associated with mercury toxicity can be complex and is yet to be fully elucidated. Hence, the present study sought to evaluate the interaction of inorganic mercury (Hg(2+)) with the ouabain-sensitive electrogenic pump in partially purified mammalian brain membrane preparations. The results show that Hg(2+) significantly inhibited the transmembrane enzyme in a concentration dependent manner. In addition, Hg(2+) exerts its inhibitory effect on the activity of the enzyme by interacting with groups at the adenosine triphosphate (ATP), Na(+) and K(+) binding sites. However, preincubation of the enzyme with exogenous monothiols, cysteine, prevented the inhibition of Hg(2+) on the pump's activity suggesting that Hg(2+) may be interacting with the thiols at the nucleotide (ATP) and cationic (Na(+) and K(+)) binding sites. In fact, our data show that Hg(2+) oxidizes sulphydryl groups in cysteine in a time dependent fashion in vitro. Finally, we speculate that the small molecular volume of Hg(2+) in comparison with the substrates (ATP, Na(+) and K(+)) of sodium pump, its possibly high reactivity and strong affinity for thiols may account for its high toxicity towards the membrane bound ouabain-sensitive electrogenic pump.
authors.affiliation: Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
authors.forename: T I
authors.initials: TI
authors.lastname: Omotayo
authors.forename: J B T
authors.initials: JB
authors.lastname: Rocha
authors.forename: E O
authors.initials: EO
authors.lastname: Ibukun
authors.forename: I J
authors.initials: IJ
authors.lastname: Kade
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002412:Cations; D008297:Male; D008628:Mercury / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry*; D010042:Ouabain / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D002412:Cations; D009711:Nucleotides; D013438:Sulfhydryl Compounds; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D008628:Mercury